Glutamate metabolism in fetus and placenta of late-gestation sheep

Abstract

Glutamate is produced by the fetal liver and taken up by the placenta. To explore the functional meaning of this exchange, the disposal rate (DR), clearance, conversion to glutamine, and decarboxylation rate of fetal plasma glutamate were studied at 129 +/- 2 days of gestation in seven fetal lambs infused via a systemic vein with L-[2,3,3,4,4-2H5]glutamate and L-[1-14C]glutamate. In two experiments, L-[1-13C]glutamate was also infused. The mean glutamate DR and clearance were 11.9 +/- 1.3 mumol.min-1.kg-1 and 200 +/- 8 ml.min-1.kg-1, respectively. The placenta extracted 88.5 +/- 0.8% of the tracer glutamate carried by the umbilical circulation and contributed to 61.3 +/- 3.2% of the glutamate DR. Most of the 14C infused as L-[1-14C]glutamate was converted to 14CO2: 37 +/- 4% by the fetus and 41 +/- 6% by the placenta. Of the labeled glutamate taken up by the placenta, 6.2 +/- 1.5% was returned to the fetus as glutamine. The glutamine-to-glutamate enrichment ratio in fetal arterial plasma was 0.066 +/- 0.008. We conclude that fetal plasma glutamate has an exceptionally high clearance because the flux of glutamate into the placenta is virtually equal to umbilical glutamate delivery rate. The main pathway of fetal plasma glutamate disposal is oxidation by placental and fetal tissues. Placental conversion of glutamate to fetal glutamine is a relatively small component of the placental metabolism of fetal glutamate.

Amino Acid Interconversions in the Fetal-Placental Unit: The Animal Model and Human Studies In Vivo

“…The fetal liver is the primary site of glutamine-to-glutamate conversion with approximately 45% of glutamine hepatic uptake converted to glutamate. However, although there is rapid conversion of plasma glutamine to plasma glutamate in the fetal liver, there is only a small reciprocal conversion of glutamate to glutamine within the placenta, whereas glutamate is mainly oxidized within the uteroplacental tissues (19).…”

Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange

“…Previous experiments have demonstrated that, under normal physiological conditions, the fetal liver takes up glutamine from the fetal circulation (13,19), that some of the glutamine taken up is converted to hepatic glutamate output (19), and that a large fraction of the glutamate delivered by the liver into the fetal circulation is taken up and oxidized by the placenta (14). These observations have led to the hypothesis that fetal hepatic glutamate output serves two important functions.…”

“…These observations have led to the hypothesis that fetal hepatic glutamate output serves two important functions. The first is to dissociate glucogenic amino acid oxidation from glucogenesis, thus allowing the fetus to maintain simultaneously a low rate of glucose production and a high rate of amino acid oxidation (14). The second is to contribute to placental glutamate oxidation, which has been linked to placental NADPH production and progesterone synthesis (10).…”

Glutamate Transport by Rcho-1 Cells Derived From Rat Placenta

“…The maternal/fetal "glutamine-glutamate cycle" has been carefully defined in the ovine model (12,13,(27)(28)(29). Maternal glutamine is transferred across the placenta to the fetal circulation, extracted by the fetal liver, and then deaminated for nitrogen utilization and release of glutamate.…”